FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 335:1363-1367 October 31, 1996 Number 18 Next

PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Insulin-like growth factor I (IGF-I) mediates the majority of the growth-promoting effects of growth hormone (GH) after birth.¹ In the prenatal period, GH does not appear to have a major influence on fetal growth, whereas IGF-I does. Infants with congenital GH deficiency and defects in the GH-receptor gene have only mild retardation of growth at birth,^2,3,4 whereas transgenic mice with a homozygous defect of the IGF-I gene (IGF-I knockout mice) have profound embryonic and postnatal growth retardation.^5,6,7 Although there is no direct evidence that IGF-I has a prominent role in human fetal growth, fetal tissues express IGF-I from an early stage, and fetal and cord serum IGF-I concentrations are correlated with fetal size.^8,9,10,11

IGF-I knockout mice also have defects in neurologic development, indicating that IGF-I may have specific roles in axonal growth and myelination.¹² In addition, neonatal mortality is substantial, suggesting that this defect may be lethal in humans.

In this report, we describe a 15-year-old boy with severe prenatal and postnatal growth failure, sensorineural deafness, and mental retardation who had a homozygous partial deletion of the IGF-I gene.

Case Report

The patient had been born at 37 weeks' gestation by cesarean section. The operation was performed because of poor fetal growth, first noted the preceding week. The pregnancy had until then been uneventful. At birth, the infant had symmetric growth retardation, with a weight of 1.4 kg (3.9 SD below the mean in normal subjects), a length of 37.8 cm (5.4 SD below the mean), and a head circumference of 27 cm (4.9 SD below the mean).¹³ The placental weight was 350 g (1.3 SD below the mean).¹⁴ The infant required nasogastric-tube feeding for three weeks. The highest serum bilirubin concentration was 12.9 mg per deciliter (221 µmol per liter), and the lowest plasma glucose concentration was 40 mg per deciliter (2.2 mmol per liter). At four weeks, he was well and was sent home.

Throughout infancy and childhood, severe growth failure continued (Figure 1A and Figure 1B). Poor responses to sound were noted, and audiograms showed profound bilateral sensorineural deafness (auditory threshold, 90 dB). The patient had moderately delayed motor development and behavioral difficulties, with hyperactivity and a short attention span.

View larger version (34K): [in this window] [in a new window]   Figure 1. Retarded Growth of a Patient with a Deletion of the IGF-I Gene. Panel A shows microcephaly and micrognathia. The growth chart (panel B) shows poor growth throughout infancy and childhood. There was no response to therapy with human growth hormone, which was administered from the age of 11 to 12.7 years (bar). The horizontal dotted lines indicate the degree of delay in bone age.

 
Studies performed at the age of eight years showed a normal male karyotype, normal thyroid function, a basal serum GH concentration of 18 ng per milliliter, and a peak serum GH concentration of 94 ng per milliliter after the administration of clonidine (both values are elevated). From the age of 11 to 12.7 years, the patient was treated with recombinant human GH in a dose of 22 U per square meter of body-surface area per week, which had no effect on his growth rate (height velocity before and during treatment, 2.5 and 2.2 cm per year, respectively) (Figure 1A and Figure 1B). At the age of 14 years, his serum IGF-I concentration was 0.05 U per milliliter (normal range for his age, 0.48 to 2.8). He was referred to our unit with a possible diagnosis of GH insensitivity.

At 15.8 years, the boy's height was 119.1 cm (6.9 SD below the mean) and his weight was 23.0 kg (6.5 SD below the mean). The body-mass index (the weight in kilograms divided by the square of the height in meters) was 16.2 (1.9 SD below the mean), the ratio of the upper to the lower segment was 1.07 (normal mean value at 15 years, 0.98) and the triceps skin-fold thickness was 6.0 cm (0.9 SD below the mean); the subscapular skin-fold thickness was normal (7.6 cm). He had microcephaly (head circumference, 47 cm) and mild dysmorphia, with micrognathia, bilateral ptosis, and a low hairline (Figure 1A and Figure 1B). There was bilateral clinodactyly (an incurved fifth finger) and a single palmar crease in the left hand. A neurologic examination showed severe bilateral hearing loss and mild myopia. He had normal-size genitalia and was in early puberty, with stage 2 genitalia and stage 1 pubic hair; the testicular volume was 4 ml bilaterally. Cardiovascular, respiratory, and abdominal examinations were normal.

The boy's parents were first cousins once removed. His mother was 154 cm tall (1.4 SD below the mean), and his father was 163 cm (1.8 SD below the mean). He had one sibling, a 10-year-old sister, who was 130 cm tall (1.0 SD below the mean). There was no family history of miscarriage or neonatal death.

Methods

We performed clinical and molecular studies after obtaining the approval of the hospital ethics committee and the informed consent of the boy's parents.

Endocrine Studies

Bone age was determined with the use of the Tanner–Whitehouse–2 RUS (radius, ulna, and small bones) method,¹⁵ and the bone mineral density at the lumbar spine was determined by dual-energy x-ray absorptiometry. An IGF-I generation test and other endocrine tests were performed as previously described.^4,16

Assays

Serum GH and insulin-like growth factor–binding protein 3 (IGFBP-3) were measured by immunoradiometric assay. Serum IGF-I was measured by radioimmunoassay,¹⁷ and undetectable values were confirmed by immunoradiometric assay (Diagnostic Systems Laboratories, Webster, Tex.). Serum IGF-II was measured by radioimmunoassay.¹⁸ Serum IGF-binding proteins were characterized by Western blotting,¹⁹ and the acid-labile subunit was determined by immunoblotting with the use of a polyclonal antibody (kindly provided by Dr. P. Lee, Diagnostic Systems Laboratories). Serum GH-binding protein was measured by high-performance liquid chromatography.²⁰ The mean (±SE) degree of specific binding of GH to the binding protein of the reference serum sample was 22.9±2.1 percent (11 determinations). All other hormones were measured by standard radioimmunoassay procedures.

Molecular Studies

DNA was obtained from peripheral-blood lymphocytes from the patient and his family. The segregation of the polymorphic dinucleotide-repeat marker D12S346 (located approximately 8 cM from the locus of the IGF-I gene²¹) was determined in the patient and his family with the use of the polymerase chain reaction (PCR) and end labeling of one primer.

Exons 3, 4, 5, and 6 of the IGF-I gene from the patient were individually amplified by PCR. A skin-biopsy specimen was obtained from the patient, and fibroblasts were grown in culture. RNA was isolated from the patient's fibroblasts, his parents' peripheral-blood lymphocytes, and normal human liver by a single-step method (RNAzol B, Biogenesis, Bournemouth, United Kingdom).²² Complementary DNA (cDNA) from the patient was obtained by reverse transcription, and IGF-I exons 3, 4, 5, and 6 were amplified with the use of PCR as previously described,²² subcloned into pGEM-T (Promega, Southampton, United Kingdom), and then sequenced (Amersham, Amersham, United Kingdom). The sequences of the oligonucleotide primers are available elsewhere (^*).

Results

Endocrine Studies

The patient's bone age was 13.5 years (delay in growth, 1.8 years). There was severe osteopenia of the lumbar region (L2–L4 bone mineral density, 4.78 SD below the mean value for age-matched normal subjects). The results of laboratory tests are shown in Table 1. Serum GH concentrations, measured every 20 minutes from 8 p.m. to 8 a.m., ranged from 2.2 to 171 ng per milliliter (peak value in normal subjects, >10 ng per milliliter) (Figure 2). The values for the serum acid-labile subunit and IGF-binding protein were normal (data not shown). Serum IGF-I, IGF-II, and IGFBP-3 values in the parents are shown in Table 2.

View this table: [in this window] [in a new window]   Table 1. Results of Laboratory Studies in a Patient with a Partial Deletion of the IGF-I Gene.

 

View larger version (2K): [in this window] [in a new window]   Figure 2. Serum Growth Hormone Concentrations in the Patient from 8 p.m. to 8 a.m., Showing Abnormally High Peaks and an Absence of Undetectable Values between Peaks.

 

View this table: [in this window] [in a new window]   Table 2. Height and Laboratory Values in Members of the Patient's Family and in Normal Subjects.

 
Neurologic Studies

Magnetic resonance imaging of the brain showed slightly enlarged occipital horns of the lateral ventricles but no other abnormalities, with an adult pattern of myelination. Electrophysiologic studies showed normal conduction times for visual evoked, somatosensory, and motor potentials.

Molecular Studies

The patient was homozygous for the D12S346 polymorphism, whereas his parents and sister were heterozygous at this locus — findings consistent with the role of the IGF-I gene in the patient's condition. Exons 4 and 5 of the patient's IGF-I gene were not amplified in repeated PCR studies (Figure 3), which is consistent with the deletion of these exons. Skin fibroblasts from the patient had a reverse-transcriptase PCR product that was 181 bp shorter than in normal subjects (Figure 4). Sequencing of this product showed that IGF-I exon 3 continued directly into exon 6, confirming the absence of exons 4 and 5 from the IGF-I cDNA (data not shown). This deletion would result in a mature IGF-I peptide truncated from 70 to 25 amino acids, followed by an additional out-of-frame nonsense sequence of eight residues and a premature stop codon. Reverse-transcriptase PCR of cDNA from both parents yielded both the abnormal product and a product of the expected size.

View larger version (4K): [in this window] [in a new window]   Figure 3. PCR Analysis of Exons 3, 4, 5, and 6 of the IGF-I Gene in the Patient (P) and a Normal Subject (N), Showing an Absence of Amplification of Exons 4 and 5 in the Patient.

 

View larger version (7K): [in this window] [in a new window]   Figure 4. Amplification of IGF-I cDNA in the Patient, Showing the Absence of Exons 4 and 5. IGF-I cDNA from the patient's skin fibroblasts and normal liver was amplified by PCR. Normally, exon 5 or exon 6 is included in the IGF-I RNA transcript. We examined the exon 3–4–6 splice variant, using one primer spanning the junction of exons 2 and 3 and another in exon 6. The results demonstrate the expected product with 397 bp in the normal tissue (lane 1) and a shorter product (216 bp) in the fibroblasts from the patient (lane 2). M denotes molecular-weight marker.

 
Discussion

Our patient had a homozygous partial deletion of the IGF-I gene. The main manifestation of the severe IGF-I deficiency was extreme growth failure in utero that persisted after birth. The patient also had profound sensorineural deafness and mental retardation.

Defects in the GH gene, the gene for the pituitary transcription factor Pit-1, and the gene for the GH-releasing–hormone receptor have all been reported to cause severe congenital GH deficiency associated with predominantly postnatal growth failure.^2,4,23 In contrast, this patient had severe intrauterine growth retardation, providing direct evidence that IGF-I plays a critical part in human fetal growth, independently of GH. Transgenic mice with a homozygous deletion of the IGF-I gene have prenatal growth failure (noted from embryonic day 13.5) and a birth weight that is 60 percent of normal.^5,6 After birth, the patient grew poorly, as do the transgenic mice, confirming the central role of IGF-I in postnatal growth, as suggested in the somatomedin hypothesis, which proposes that many of the actions of GH are derived from hepatic IGF-I.¹

Although the pattern of growth failure in this patient appears to be very similar to that in the IGF-I knockout mice, there are a number of phenotypic differences. At the patient's birth, the weight of the placenta was below average, whereas the placental size is normal with the IGF-I knockout mice. Furthermore, the IGF-I knockout mice have very small reproductive organs and are infertile in adulthood, whereas our patient has normal-size genitalia and is progressing through puberty, albeit rather late.

A comparison of our patient with patients who have GH insensitivity (Laron dwarfism), who also have high serum GH concentrations and low serum IGF-I concentrations, provides valuable information on the effects of GH that are not mediated by IGF-I. The patient's serum IGFBP-3 and acid-labile subunit concentrations were normal — findings in support of recent studies showing that these peptides are controlled independently of IGF-I in humans.^24,25,26,27 Patients with GH insensitivity are sensitive to insulin and have episodes of hypoglycemia, especially during infancy.²⁸ Our patient has not had hypoglycemia, perhaps because of a resistance to insulin resulting from excess GH secretion. In addition, his bone age has been only minimally delayed, supporting the hypothesis that GH stimulates bone maturation directly.²⁹

Deafness, mental retardation, and microcephaly are not features of congenital GH deficiency or insensitivity.²⁸ Studies in both IGF-I knockout mice and mice with an overexpression of the IGF-I gene suggest that IGF-I has a role in the central nervous system.^7,30 IGF-I knockout mice have small brains, hypomyelination, and loss of certain subtypes of neurons.⁷ Our patient appeared to have normal myelination, but his neurologic abnormalities may indicate that prenatal IGF-I is important in other aspects of central nervous system development in humans.

An intriguing finding was the short stature of the patient's parents and their borderline low serum IGF-I concentrations. The finding of a heterozygous effect of the IGF-I gene would indicate that this genotype could be prevalent in the population of children with idiopathic short stature, as has been suggested for heterozygous defects of the GH receptor.³¹

In summary, we have described a child with a homozygous defect of the IGF-I gene. This defect was associated with growth failure before and after birth, indicating that IGF-I is critical for prenatal as well as postnatal growth. In addition, the patient's neurologic development was abnormal, suggesting the role of IGF-I in the development of the central nervous system.

Supported by grants from Pharmacia Peptide Hormones and the Adint Trust (to Dr. Woods) and the Joint Research Board of St. Bartholomew's Hospital (to Dr. Camacho–Hübner).

We are indebted to Denis Barter, of Kings Lynn Hospital, Norfolk, United Kingdom, for referring the patient to us; to Shern J. Chew for helpful comments; to Sami Medbak, Martin Yateman, and Farhana Abdulla for their assistance with the laboratory studies; and to Caroline Nulty for her assistance as research nurse.

^* See NAPS document no. 05341 for one page of supplementary material. To order, contact NAPS c/o Microfiche Publications, 248 Hempstead Tpk., West Hempstead, NY 11552.

Source Information

From the Departments of Endocrinology (K.A.W., M.O.S.) and Chemical Endocrinology (C.C.-H., A.J.L.C.), St. Bartholomew's Hospital, London.

Address reprint requests to Dr. Clark at the Department of Chemical Endocrinology, 51-53 Bartholomew Close, St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom.

References

1. Salmon WD Jr, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 1957;49:825-836. [Medline]
2. Woods KA, Weber A, Clark AJL. The molecular pathology of pituitary hormone deficiency and resistance. In: Thakker R, ed. Genetic and molecular biological aspects of endocrine disease. London: Baillière Tindall, 1995:453-87.
3. Gluckman PD, Gunn AJ, Wray A, et al. Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure: the International Board of the Kabi Pharmacia International Growth Study. J Pediatr 1992;121:920-923. [CrossRef][Medline]
4. Savage MO, Blum WF, Ranke MB, et al. Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome). J Clin Endocrinol Metab 1993;77:1465-1471. [Abstract]
5. Liu J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 1993;75:59-72. [Medline]
6. Baker J, Liu J-P, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1993;75:73-82. [CrossRef][Medline]
7. Powell-Braxton L, Hollingshead P, Warburton C, et al. IGF-I is required for normal embryonic growth in mice. Genes Dev 1993;7:2609-2617. [Free Full Text]
8. Han VK, Lund PK, Lee DC, D'Ercole AJ. Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: identification, characterization, and tissue distribution. J Clin Endocrinol Metab 1988;66:422-429. [Abstract]
9. Lassarre C, Hardouin S, Daffos F, Forestier F, Frankenne F, Binoux M. Serum insulin-like growth factors and insulin-like growth factor binding proteins in the human fetus: relationships with growth in normal subjects and in subjects with intrauterine growth retardation. Pediatr Res 1991;29:219-225.
10. Gluckman PD. The endocrine regulation of fetal growth in late gestation: the role of insulin-like growth factors. J Clin Endocrinol Metab 1995;80:1047-1050. [CrossRef][Medline]
11. Giudice LC, de Zegher F, Gargosky SE, et al. Insulin-like growth factors and their binding proteins in the term and preterm human fetus and neonate with normal and extremes of intrauterine growth. J Clin Endocrinol Metab 1995;80:1548-1555. [Free Full Text]
12. Beck KD, Powell-Braxton L, Widmer H-R, Valverde J, Hefti F. Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons. Neuron 1995;14:717-730. [CrossRef][Medline]
13. Freeman JV, Cole TJ, Chinn S, Jones PRM, White EM, Preece MA. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995;73:17-24. [Abstract]
14. Naeye RL. Do placental weights have clinical significance? Hum Pathol 1987;18:387-391. [Medline]
15. Cameron N. The methods of auxological anthropometry. In: Falkner F, Tanner JM, eds. Human growth. Vol. 2. Postnatal growth. New York: Plenum Press, 1978:35-90.
16. Trainer PJ, Besser GM. The Barts endocrine protocols. London: Churchill Livingstone, 1995.
17. Morrell DJ, Dadi H, More J, et al. A monoclonal antibody to human insulin-like growth factor-I: characterization, use in radioimmunoassay and effect on the biological activities of the growth factor. J Mol Endocrinol 1989;2:201-206. [Free Full Text]
18. Blum WF, Ranke MB, Bierich JR. A specific radioimmunoassay for insulin-like growth factor II: the interference of IGF binding proteins can be blocked by excess IGF-I. Acta Endocrinol (Copenh) 1988;118:374-380. [Free Full Text]
19. Hossenlopp P, Seurin D, Segovia-Quinson B, Hardouin S, Binoux M. Analysis of serum insulin-like growth factor binding proteins using Western blotting: use of the method for titration of the binding proteins and competitive binding studies. Anal Biochem 1986;154:138-143. [CrossRef][Medline]
20. Amselem S, Duquesnoy P, Attree O, et al. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 1989;321:989-995. [Abstract]
21. Brissenden JE, Ullrich A, Francke U. Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature 1984;310:781-784. [CrossRef][Medline]
22. Chew SJ, Lavender P, Clark AJL, Ross RJM. An alternatively spliced human insulin-like growth factor-I transcript with hepatic tissue expression that diverts away from the mitogenic IBE1 peptide. Endocrinology 1995;136:1939-1944. [Abstract]
23. Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr, Leibel RL. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 1996;12:88-90. [CrossRef][Medline]
24. Gargosky SE, Wilson KF, Fielder PJ, et al. The composition and distribution of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in the serum of growth hormone receptor-deficient patients: effects of IGF-I therapy on IGFBP-3. J Clin Endocrinol Metab 1993;77:1683-1689. [Abstract]
25. Hardouin S, Gourmelen M, Noguiez P, et al. Molecular forms of serum insulin-like growth factor (IGF)-binding proteins in man: relationships with growth hormone and IGFs and physiological significance. J Clin Endocrinol Metab 1989;69:1291-1301. [Abstract]
26. Zapf J, Hauri C, Waldvogel M, et al. Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypo-physectomized and diabetic rats. Proc Natl Acad Sci U S A 1989;86:3813-3817. [Free Full Text]
27. Baxter RC. Circulating levels and molecular distribution of the acid-labile (alpha) subunit of the high molecular weight insulin-like growth factor-binding protein complex. J Clin Endocrinol Metab 1990;70:1347-1353. [Abstract]
28. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J. Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev 1994;15:369-390. [CrossRef][Medline]
29. Isaksson OG, Lindahl A, Nilsson A, Isgaard J. Mechanism of the stimulatory effect of growth hormone on longitudinal bone growth. Endocr Rev 1987;8:426-438. [CrossRef][Medline]
30. D'Ercole AJ. Expression of insulin-like growth factor-I in transgenic mice. Ann N Y Acad Sci 1993;692:149-160. [Medline]
31. Goddard AD, Covello R, Luoh S-M, et al. Mutations of the growth hormone receptor in children with idiopathic short stature. N Engl J Med 1995;333:1093-1098. [Free Full Text]

PDF Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

This article has been cited by other articles:

• Frazier-Bowers, S., Rincon-Rodriguez, R., Zhou, J., Alexander, K., Lange, E. (2009). Evidence of Linkage in a Hispanic Cohort with a Class III Dentofacial Phenotype. JDR 88: 56-60 [Abstract] [Full Text]  
• Wu, S., Fadoju, D., Rezvani, G., De Luca, F. (2008). Stimulatory Effects of Insulin-like Growth Factor-I on Growth Plate Chondrogenesis Are Mediated by Nuclear Factor-{kappa}B p65. J. Biol. Chem. 283: 34037-34044 [Abstract] [Full Text]  
• Murphy, R., Baptista, J., Holly, J., Umpleby, A. M., Ellard, S., Harries, L. W., Crolla, J., Cundy, T., Hattersley, A. T. (2008). Severe Intrauterine Growth Retardation and Atypical Diabetes Associated with a Translocation Breakpoint Disrupting Regulation of the Insulin-Like Growth Factor 2 Gene. J. Clin. Endocrinol. Metab. 93: 4373-4380 [Abstract] [Full Text]  
• Laviola, L., Natalicchio, A., Perrini, S., Giorgino, F. (2008). Abnormalities of IGF-I signaling in the pathogenesis of diseases of the bone, brain, and fetoplacental unit in humans. Am. J. Physiol. Endocrinol. Metab. 295: E991-E999 [Abstract] [Full Text]  
• Giustina, A., Mazziotti, G., Canalis, E. (2008). Growth Hormone, Insulin-Like Growth Factors, and the Skeleton. Endocr. Rev. 29: 535-559 [Abstract] [Full Text]  
• van Duyvenvoorde, H A, Kempers, M J E, Twickler, T. B, van Doorn, J, Gerver, W J, Noordam, C, Losekoot, M, Karperien, M, Wit, J M, Hermus, A R M M (2008). Homozygous and heterozygous expression of a novel mutation of the acid-labile subunit. Eur J Endocrinol 159: 113-120 [Abstract] [Full Text]  
• Gauguin, L., Delaine, C., Alvino, C. L., McNeil, K. A., Wallace, J. C., Forbes, B. E., De Meyts, P. (2008). Alanine Scanning of a Putative Receptor Binding Surface of Insulin-like Growth Factor-I. J. Biol. Chem. 283: 20821-20829 [Abstract] [Full Text]  
• Forbes, K., Westwood, M., Baker, P. N., Aplin, J. D. (2008). Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta. Am. J. Physiol. Cell Physiol. 294: C1313-C1322 [Abstract] [Full Text]  
• Sachdev, D., Yee, D. (2008). Disrupting Insulin-Like Growth Factor Signaling as a Potential Cancer Therapy. aacredbook 2008: 39-58 [Abstract] [Full Text]  
• Suh, Y., Atzmon, G., Cho, M.-O., Hwang, D., Liu, B., Leahy, D. J., Barzilai, N., Cohen, P. (2008). Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc. Natl. Acad. Sci. USA 105: 3438-3442 [Abstract] [Full Text]  
• Ryan, P. D., Goss, P. E. (2008). The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer. The Oncologist 13: 16-24 [Abstract] [Full Text]  
• Coutinho, D. C., Coletta, R. R. D., Costa, E. M. F., Pachi, P. R., Boguszewski, M. C. S., Damiani, D., Mendonca, B. B., Arnhold, I. J. P., Jorge, A. A. L. (2007). Polymorphisms Identified in the Upstream Core Polyadenylation Signal of IGF1 Gene Exon 6 Do Not Cause Pre- and Postnatal Growth Impairment. J. Clin. Endocrinol. Metab. 92: 4889-4892 [Abstract] [Full Text]  
• DiGirolamo, D. J., Mukherjee, A., Fulzele, K., Gan, Y., Cao, X., Frank, S. J., Clemens, T. L. (2007). Mode of Growth Hormone Action in Osteoblasts. J. Biol. Chem. 282: 31666-31674 [Abstract] [Full Text]  
• Bannink, E. M. N., van Doorn, J., Mulder, P. G. H., Hokken-Koelega, A. C. S. (2007). Free/Dissociable Insulin-Like Growth Factor (IGF)-I, Not Total IGF-I, Correlates with Growth Response during Growth Hormone Treatment in Children Born Small for Gestational Age. J. Clin. Endocrinol. Metab. 92: 2992-3000 [Abstract] [Full Text]  
• Walenkamp, M J E, Wit, J M (2007). Genetic disorders in the GH IGF-I axis in mouse and man. Eur J Endocrinol 157: S15-S26 [Abstract] [Full Text]  
• Rosenfeld, R. G (2007). IGF-I therapy in growth disorders. Eur J Endocrinol 157: S57-S60 [Abstract] [Full Text]  
• Cohen, P., Rogol, A. D., Howard, C. P., Bright, G. M., Kappelgaard, A.-M., Rosenfeld, R. G., on behalf of the American Norditropin Study Group, (2007). Insulin Growth Factor-Based Dosing of Growth Hormone Therapy in Children: A Randomized, Controlled Study. J. Clin. Endocrinol. Metab. 92: 2480-2486 [Abstract] [Full Text]  
• Dunger, D. B., Petry, C. J., Ong, K. K. (2007). Genetics of Size at Birth. Diabetes Care 30: S150-S155 [Full Text]  
• Fang, P., Riedl, S., Amselem, S., Pratt, K. L., Little, B. M., Haeusler, G., Hwa, V., Frisch, H., Rosenfeld, R. G. (2007). Primary Growth Hormone (GH) Insensitivity and Insulin-Like Growth Factor Deficiency Caused by Novel Compound Heterozygous Mutations of the GH Receptor Gene: Genetic and Functional Studies of Simple and Compound Heterozygous States. J. Clin. Endocrinol. Metab. 92: 2223-2231 [Abstract] [Full Text]  
• Dissanayake, V.H.W., Tower, C., Broderick, A., Stocker, L.J., Seneviratne, H.R., Jayasekara, R.W., Kalsheker, N., Pipkin, F.B., Morgan, L. (2007). Polymorphism in the epidermal growth factor gene is associated with birthweight in Sinhalese and white Western Europeans. Mol Hum Reprod 13: 425-429 [Abstract] [Full Text]  
• Sutter, N. B., Bustamante, C. D., Chase, K., Gray, M. M., Zhao, K., Zhu, L., Padhukasahasram, B., Karlins, E., Davis, S., Jones, P. G., Quignon, P., Johnson, G. S., Parker, H. G., Fretwell, N., Mosher, D. S., Lawler, D. F., Satyaraj, E., Nordborg, M., Lark, K. G., Wayne, R. K., Ostrander, E. A. (2007). A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science 316: 112-115 [Abstract] [Full Text]  
• Saenger, P., Czernichow, P., Hughes, I., Reiter, E. O. (2007). Small for Gestational Age: Short Stature and Beyond. Endocr. Rev. 28: 219-251 [Abstract] [Full Text]  
• Lunde, A., Melve, K. K., Gjessing, H. K., Skjaerven, R., Irgens, L. M. (2007). Genetic and Environmental Influences on Birth Weight, Birth Length, Head Circumference, and Gestational Age by Use of Population-based Parent-Offspring Data. Am J Epidemiol 165: 734-741 [Abstract] [Full Text]  
• Clayton, P. E., Cianfarani, S., Czernichow, P., Johannsson, G., Rapaport, R., Rogol, A. (2007). Management of the Child Born Small for Gestational Age through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J. Clin. Endocrinol. Metab. 92: 804-810 [Abstract] [Full Text]  
• Walenkamp, M. J E, Vidarsdottir, S., Pereira, A. M, Karperien, M., van Doorn, J., van Duyvenvoorde, H. A, Breuning, M. H, Roelfsema, F., Kruithof, M F., van Dissel, J., Janssen, R., Wit, J. M, Romijn, J. A (2007). Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation. Eur J Endocrinol 156: 155-165 [Abstract] [Full Text]  
• Sachdev, D., Yee, D. (2007). Disrupting insulin-like growth factor signaling as a potential cancer therapy. Molecular Cancer Therapeutics 6: 1-12 [Abstract] [Full Text]  
• Moerth, C., Schneider, M. R., Renner-Mueller, I., Blutke, A., Elmlinger, M. W., Erben, R. G., Camacho-Hubner, C., Hoeflich, A., Wolf, E. (2007). Postnatally Elevated Levels of Insulin-Like Growth Factor (IGF)-II Fail to Rescue the Dwarfism of IGF-I-Deficient Mice except Kidney Weight. Endocrinology 148: 441-451 [Abstract] [Full Text]  
• Rosenbloom, A. L., Guevara-Aguirre, J. (2006). Reclassification of Insulin-Like Growth Factor I Production and Action Disorders. J. Clin. Endocrinol. Metab. 91: 4232-4234 [Abstract] [Full Text]  
• Cohen, P. (2006). Problems with Reclassification of Insulin-Like Growth Factor I Production and Action Disorders. J. Clin. Endocrinol. Metab. 91: 4235-4236 [Abstract] [Full Text]  
• Zhang, H., Yee, D. (2006). Is the type I insulin-like growth factor receptor a therapeutic target in endometrial cancer?. Clin. Cancer Res. 12: 6323-6325 [Full Text]  
• Walenkamp, M. J. E., van der Kamp, H. J., Pereira, A. M., Kant, S. G., van Duyvenvoorde, H. A., Kruithof, M. F., Breuning, M. H., Romijn, J. A., Karperien, M., Wit, J. M. (2006). A Variable Degree of Intrauterine and Postnatal Growth Retardation in a Family with a Missense Mutation in the Insulin-Like Growth Factor I Receptor. J. Clin. Endocrinol. Metab. 91: 3062-3070 [Abstract] [Full Text]  
• Rogers, I., Metcalfe, C., Gunnell, D., Emmett, P., Dunger, D., Holly, J., and the Avon Longitudinal Study of Parents and Chi, (2006). Insulin-Like Growth Factor-I and Growth in Height, Leg Length, and Trunk Length between Ages 5 and 10 Years. J. Clin. Endocrinol. Metab. 91: 2514-2519 [Abstract] [Full Text]  
• Hiendleder, S., Wirtz, M., Mund, C., Klempt, M., Reichenbach, H.-D., Stojkovic, M., Weppert, M., Wenigerkind, H., Elmlinger, M., Lyko, F., Schmitz, O. J., Wolf, E. (2006). Tissue-Specific Effects of In Vitro Fertilization Procedures on Genomic Cytosine Methylation Levels in Overgrown and Normal Sized Bovine Fetuses. Biol. Reprod. 75: 17-23 [Abstract] [Full Text]  
• Svensson, J, Diez, M, Engel, J, Wass, C, Tivesten, A, Jansson, J-O, Isaksson, O, Archer, T, Hokfelt, T, Ohlsson, C (2006). Endocrine, liver-derived IGF-I is of importance for spatial learning and memory in old mice.. J Endocrinol 189: 617-627 [Abstract] [Full Text]  
• Schlueter, P. J., Royer, T., Farah, M. H., Laser, B., Chan, S. J., Steiner, D. F., Duan, C. (2006). Gene duplication and functional divergence of the zebrafish insulin-like growth factor 1 receptors. FASEB J. 20: 1230-1232 [Abstract] [Full Text]  
• Hwa, V., Haeusler, G., Pratt, K. L., Little, B. M., Frisch, H., Koller, D., Rosenfeld, R. G. (2006). Total Absence of Functional Acid Labile Subunit, Resulting in Severe Insulin-Like Growth Factor Deficiency and Moderate Growth Failure. J. Clin. Endocrinol. Metab. 91: 1826-1831 [Abstract] [Full Text]  
• Chia, D. J., Subbian, E., Buck, T. M., Hwa, V., Rosenfeld, R. G., Skach, W. R., Shinde, U., Rotwein, P. (2006). Aberrant Folding of a Mutant Stat5b Causes Growth Hormone Insensitivity and Proteasomal Dysfunction. J. Biol. Chem. 281: 6552-6558 [Abstract] [Full Text]  
• Chellakooty, M., Juul, A., Boisen, K. A., Damgaard, I. N., Kai, C. M., Schmidt, I. M., Petersen, J. H., Skakkebaek, N. E., Main, K. M. (2006). A Prospective Study of Serum Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3 in 942 Healthy Infants: Associations with Birth Weight, Gender, Growth Velocity, and Breastfeeding. J. Clin. Endocrinol. Metab. 91: 820-826 [Abstract] [Full Text]  
• Mohan, S. (2006). Riddle of Estrogen Regulation of IGF-I Action and Periosteal Bone Formation. IBMS BoneKEy 3: 17-19 [Full Text]  
• Miller, B. S., Yee, D. (2005). Type I Insulin-like Growth Factor Receptor as a Therapeutic Target in Cancer. Cancer Res. 65: 10123-10127 [Abstract] [Full Text]  
• Iida, K, Rosen, C J, Ackert-Bicknell, C, Thorner, M O (2005). Genetic differences in the IGF-I gene among inbred strains of mice with different serum IGF-I levels. J Endocrinol 186: 481-489 [Abstract] [Full Text]  
• Svensson, J., Soderpalm, B., Sjogren, K., Engel, J., Ohlsson, C. (2005). Liver-derived IGF-I regulates exploratory activity in old mice. Am. J. Physiol. Endocrinol. Metab. 289: E466-E473 [Abstract] [Full Text]  
• Kawashima, Y., Kanzaki, S., Yang, F., Kinoshita, T., Hanaki, K., Nagaishi, J.-i., Ohtsuka, Y., Hisatome, I., Ninomoya, H., Nanba, E., Fukushima, T., Takahashi, S.-I. (2005). Mutation at Cleavage Site of Insulin-Like Growth Factor Receptor in a Short-Stature Child Born with Intrauterine Growth Retardation. J. Clin. Endocrinol. Metab. 90: 4679-4687 [Abstract] [Full Text]  
• Hwa, V., Little, B., Adiyaman, P., Kofoed, E. M., Pratt, K. L., Ocal, G., Berberoglu, M., Rosenfeld, R. G. (2005). Severe Growth Hormone Insensitivity Resulting from Total Absence of Signal Transducer and Activator of Transcription 5b. J. Clin. Endocrinol. Metab. 90: 4260-4266 [Abstract] [Full Text]  
• Morimoto, L. M., Newcomb, P. A., White, E., Bigler, J., Potter, J. D. (2005). Insulin-like Growth Factor Polymorphisms and Colorectal Cancer Risk. Cancer Epidemiol. Biomarkers Prev. 14: 1204-1211 [Abstract] [Full Text]  
• Walenkamp, M. J. E., Karperien, M., Pereira, A. M., Hilhorst-Hofstee, Y., van Doorn, J., Chen, J. W., Mohan, S., Denley, A., Forbes, B., van Duyvenvoorde, H. A., van Thiel, S. W., Sluimers, C. A., Bax, J. J., de Laat, J. A. P. M., Breuning, M. B, Romijn, J. A., Wit, J. M. (2005). Homozygous and Heterozygous Expression of a Novel Insulin-Like Growth Factor-I Mutation. J. Clin. Endocrinol. Metab. 90: 2855-2864 [Abstract] [Full Text]  
• Gohlke, B. C., Huber, A., Hecher, K., Fimmers, R., Bartmann, P., Roth, C. L. (2005). Fetal Insulin-Like Growth Factor (IGF)-I, IGF-II, and Ghrelin in Association with Birth Weight and Postnatal Growth in Monozygotic Twins with Discordant Growth. J. Clin. Endocrinol. Metab. 90: 2270-2274 [Abstract] [Full Text]  
• Veldhuis, J. D., Anderson, S. M., Iranmanesh, A., Bowers, C. Y. (2005). Testosterone Blunts Feedback Inhibition of Growth Hormone Secretion by Experimentally Elevated Insulin-Like Growth Factor-I Concentrations. J. Clin. Endocrinol. Metab. 90: 1613-1617 [Abstract] [Full Text]  
• Laviola, L., Perrini, S., Belsanti, G., Natalicchio, A., Montrone, C., Leonardini, A., Vimercati, A., Scioscia, M., Selvaggi, L., Giorgino, R., Greco, P., Giorgino, F. (2005). Intrauterine Growth Restriction in Humans Is Associated with Abnormalities in Placental Insulin-Like Growth Factor Signaling. Endocrinology 146: 1498-1505 [Abstract] [Full Text]  
• Sun, L. Y., Evans, M. S., Hsieh, J., Panici, J., Bartke, A. (2005). Increased Neurogenesis in Dentate Gyrus of Long-Lived Ames Dwarf Mice. Endocrinology 146: 1138-1144 [Abstract] [Full Text]  
• Kajimura, S., Aida, K., Duan, C. (2005). From the Cover: Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc. Natl. Acad. Sci. USA 102: 1240-1245 [Abstract] [Full Text]  
• Mullis, P. E (2005). Genetic control of growth. Eur J Endocrinol 152: 11-31 [Abstract] [Full Text]  
• Hayati, A R, Cheah, F C, Yong, J F, Tan, A E, Norizah, W M (2004). The role of serum insulin-like growth factor I (IGF-I) in neonatal outcome. J. Clin. Pathol. 57: 1299-1301 [Abstract] [Full Text]  
• Brodsky, D., Christou, H. (2004). Current Concepts in Intrauterine Growth Restriction. J Intensive Care Med 19: 307-319 [Abstract]  
• Arends, N. J.T., Boonstra, V. H., Hokken-Koelega, A. C.S. (2004). Head Circumference and Body Proportions Before and During Growth Hormone Treatment in Short Children Who Were Born Small for Gestational Age. Pediatrics 114: 683-690 [Abstract] [Full Text]  
• Laron, Z. (2004). Laron Syndrome (Primary Growth Hormone Resistance or Insensitivity): The Personal Experience 1958-2003. J. Clin. Endocrinol. Metab. 89: 1031-1044 [Abstract] [Full Text]  
• Bazaes, R. A., Alegria, A., Pittaluga, E., Avila, A., Iniguez, G., Mericq, V. (2004). Determinants of Insulin Sensitivity and Secretion in Very-Low-Birth-Weight Children. J. Clin. Endocrinol. Metab. 89: 1267-1272 [Abstract] [Full Text]  
• Domene, H. M., Bengolea, S. V., Martinez, A. S., Ropelato, M. G., Pennisi, P., Scaglia, P., Heinrich, J. J., Jasper, H. G. (2004). Deficiency of the Circulating Insulin-like Growth Factor System Associated with Inactivation of the Acid-Labile Subunit Gene. NEJM 350: 570-577 [Full Text]  
• Hwa, V., Little, B., Kofoed, E. M., Rosenfeld, R. G. (2004). Transcriptional Regulation of Insulin-like Growth Factor-I by Interferon-{gamma} Requires STAT-5b. J. Biol. Chem. 279: 2728-2736 [Abstract] [Full Text]  
• Mitchell, S. M. S., Hattersley, A. T., Knight, B., Turner, T., Metcalf, B. S., Voss, L. D., Davies, D., McCarthy, A., Wilkin, T. J., Smith, G. D., Ben-Shlomo, Y., Frayling, T. M. (2004). Lack of Support for a Role of the Insulin Gene Variable Number of Tandem Repeats Minisatellite (INS-VNTR) Locus in Fetal Growth or Type 2 Diabetes-Related Intermediate Traits in United Kingdom Populations. J. Clin. Endocrinol. Metab. 89: 310-317 [Abstract] [Full Text]  
• Bernard, F., Picard, C., Cormier-Daire, V., Eidenschenk, C., Pinto, G., Bustamante, J.-C., Jouanguy, E., Teillac-Hamel, D., Colomb, V., Funck-Brentano, I., Pascal, V., Vivier, E., Fischer, A., Le Deist, F., Casanova, J.-L. (2004). A Novel Developmental and Immunodeficiency Syndrome Associated With Intrauterine Growth Retardation and a Lack of Natural Killer Cells. Pediatrics 113: 136-141 [Abstract] [Full Text]  
• Abuzzahab, M. J., Schneider, A., Goddard, A., Grigorescu, F., Lautier, C., Keller, E., Kiess, W., Klammt, J., Kratzsch, J., Osgood, D., Pfaffle, R., Raile, K., Seidel, B., Smith, R. J., Chernausek, S. D., the Intrauterine Growth Retardation (IUGR) Study G, (2003). IGF-I Receptor Mutations Resulting in Intrauterine and Postnatal Growth Retardation. NEJM 349: 2211-2222 [Abstract] [Full Text]  
• van der Eerden, B. C. J., Karperien, M., Wit, J. M. (2003). Systemic and Local Regulation of the Growth Plate. Endocr. Rev. 24: 782-801 [Abstract] [Full Text]  
• Johnston, L. B., Dahlgren, J., Leger, J., Gelander, L., Savage, M. O., Czernichow, P., Wikland, K. A., Clark, A. J. L. (2003). Association between Insulin-Like Growth Factor I (IGF-I) Polymorphisms, Circulating IGF-I, and Pre- and Postnatal Growth in Two European Small for Gestational Age Populations. J. Clin. Endocrinol. Metab. 88: 4805-4810 [Abstract] [Full Text]  
• Lin, D., Smith, M. A., Champagne, C., Elter, J., Beck, J., Offenbacher, S. (2003). Porphyromonas gingivalis Infection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice. Infect. Immun. 71: 5156-5162 [Abstract] [Full Text]  
• Schubert, M., Brazil, D. P., Burks, D. J., Kushner, J. A., Ye, J., Flint, C. L., Farhang-Fallah, J., Dikkes, P., Warot, X. M., Rio, C., Corfas, G., White, M. F. (2003). Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation. J. Neurosci. 23: 7084-7092 [Abstract] [Full Text]  
• Wu, Y., Cui, K., Miyoshi, K., Hennighausen, L., Green, J. E., Setser, J., LeRoith, D., Yakar, S. (2003). Reduced Circulating Insulin-like Growth Factor I Levels Delay the Onset of Chemically and Genetically Induced Mammary Tumors. Cancer Res. 63: 4384-4388 [Abstract] [Full Text]  
• Lee, P. A., Kendig, J. W., Kerrigan, J. R. (2003). Persistent Short Stature, Other Potential Outcomes, and the Effect of Growth Hormone Treatment in Children Who Are Born Small for Gestational Age. Pediatrics 112: 150-162 [Full Text]  
• Woelfle, J., Billiard, J., Rotwein, P. (2003). Acute Control of Insulin-like Growth Factor-I Gene Transcription by Growth Hormone through Stat5b. J. Biol. Chem. 278: 22696-22702 [Abstract] [Full Text]  
• Mohan, S., Richman, C., Guo, R., Amaar, Y., Donahue, L. R., Wergedal, J., Baylink, D. J. (2003). Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms. Endocrinology 144: 929-936 [Abstract] [Full Text]  
• Kajantie, E., Fall, C. H. D., Seppala, M., Koistinen, R., Dunkel, L., Yliharsila, H., Osmond, C., Andersson, S., Barker, D. J. P., Forsen, T., Holt, R. I. G., Phillips, D. I. W., Eriksson, J. (2003). Serum Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-1 in Elderly People: Relationships with Cardiovascular Risk Factors, Body Composition, Size at Birth, and Childhood Growth. J. Clin. Endocrinol. Metab. 88: 1059-1065 [Abstract] [Full Text]  
• Huang, J.-X., Feldmeier, M., Shui, Y.-B., Beebe, D. C. (2003). Evaluation of Fibroblast Growth Factor Signaling during Lens Fiber Cell Differentiation. IOVS 44: 680-690 [Abstract] [Full Text]  
• Frago, L. M., Canon, S., de la Rosa, E. J., Leon, Y., Varela-Nieto, I. (2003). Programmed cell death in the developing inner ear is balanced by nerve growth factor and insulin-like growth factor I. J. Cell Sci. 116: 475-486 [Abstract] [Full Text]  
• Hellstrom, A., Carlsson, B., Niklasson, A., Segnestam, K., Boguszewski, M., de Lacerda, L., Savage, M., Svensson, E., Smith, L., Weinberger, D., Albertsson Wikland, K., Laron, Z. (2002). IGF-I Is Critical for Normal Vascularization of the Human Retina. J. Clin. Endocrinol. Metab. 87: 3413-3416 [Abstract] [Full Text]  
• Maures, T. J., Duan, C. (2002). Structure, Developmental Expression, and Physiological Regulation of Zebrafish IGF Binding Protein-1. Endocrinology 143: 2722-2731 [Abstract] [Full Text]  
• Kajantie, E., Dunkel, L., Rutanen, E.-M., Seppala, M., Koistinen, R., Sarnesto, A., Andersson, S. (2002). IGF-I, IGF Binding Protein (IGFBP)-3, Phosphoisoforms of IGFBP-1, and Postnatal Growth in Very Low Birth Weight Infants. J. Clin. Endocrinol. Metab. 87: 2171-2179 [Abstract] [Full Text]  
• Butler, A. A., Yakar, S., LeRoith, D. (2002). Insulin-Like Growth Factor-I: Compartmentalization Within the Somatotropic Axis?. Physiology 17: 82-85 [Abstract] [Full Text]  
• Johnston, L B, Clark, A J L, Savage, M O (2002). Genetic factors contributing to birth weight. Arch. Dis. Child. Fetal Neonatal Ed. 86: F2-3 [Full Text]  
• Nakae, J., Kido, Y., Accili, D. (2001). Distinct and Overlapping Functions of Insulin and IGF-I Receptors. Endocr. Rev. 22: 818-835 [Abstract] [Full Text]  
• Ducos, B., Cabrol, S., Houang, M., Perin, L., Holzenberger, M., Le Bouc, Y. (2001). IGF Type 1 Receptor Ligand Binding Characteristics Are Altered in a Subgroup of Children with Intrauterine Growth Retardation. J. Clin. Endocrinol. Metab. 86: 5516-5524 [Abstract] [Full Text]  
• Wallenius, K., Sjogren, K., Peng, X.-D., Park, S., Wallenius, V., Liu, J.-L., Umaerus, M., Wennbo, H., Isaksson, O., Frohman, L., Kineman, R., Ohlsson, C., Jansson, J.-O. (2001). Liver-Derived IGF-I Regulates GH Secretion at the Pituitary Level in Mice. Endocrinology 142: 4762-4770 [Abstract] [Full Text]  
• Laron, Z (2001). Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol. Pathol. 54: 311-316 [Abstract] [Full Text]  
• Camarero, G., Avendano, C., Fernandez-Moreno, C., Villar, A., Contreras, J., de Pablo, F., Pichel, J. G., Varela-Nieto, I. (2001). Delayed Inner Ear Maturation and Neuronal Loss in Postnatal Igf-1-Deficient Mice. J. Neurosci. 21: 7630-7641 [Abstract] [Full Text]  
• Larroque, B., Bertrais, S., Czernichow, P., Leger, J. (2001). School Difficulties in 20-Year-Olds Who Were Born Small for Gestational Age at Term in a Regional Cohort Study. Pediatrics 108: 111-115 [Abstract] [Full Text]  
• Popovici, R. M., Lu, M., Bhatia, S., Faessen, G. H., Giaccia, A. J., Giudice, L. C. (2001). Hypoxia Regulates Insulin-Like Growth Factor-Binding Protein 1 in Human Fetal Hepatocytes in Primary Culture: Suggestive Molecular Mechanisms for in Utero Fetal Growth Restriction Caused by Uteroplacental Insufficiency. J. Clin. Endocrinol. Metab. 86: 2653-2659 [Abstract] [Full Text]  
• Miyakoshi, N., Qin, X., Kasukawa, Y., Richman, C., Srivastava, A. K., Baylink, D. J., Mohan, S. (2001). Systemic Administration of Insulin-Like Growth Factor (IGF)-Binding Protein-4 (IGFBP-4) Increases Bone Formation Parameters in Mice by Increasing IGF Bioavailability via an IGFBP-4 Protease-Dependent Mechanism. Endocrinology 142: 2641-2648 [Abstract] [Full Text]  
• De Benedetti, F., Pignatti, P., Vivarelli, M., Meazza, C., Ciliberto, G., Savino, R., Martini, A. (2001). In Vivo Neutralization of Human IL-6 (hIL-6) Achieved by Immunization of hIL-6-Transgenic Mice with a hIL-6 Receptor Antagonist. J. Immunol. 166: 4334-4340 [Abstract] [Full Text]  
• Ballinger, A.B., Camacho-Hubner, C., Croft, N.M. (2001). Growth failure and intestinal inflammation. QJM 94: 121-125 [Full Text]  
• Le Roith, D., Bondy, C., Yakar, S., Liu, J.-L., Butler, A. (2001). The Somatomedin Hypothesis: 2001. Endocr. Rev. 22: 53-74 [Abstract] [Full Text]  
• Vanhala, R., Turpeinen, U., Riikonen, R. (2000). Insulin-Like Growth Factor-I in Cerebrospinal Fluid and Serum in Rett Syndrome. J Child Neurol 15: 797-802 [Abstract]  
• Liu, J.-L., Yakar, S., LeRoith, D. (2000). Mice Deficient in Liver Production of Insulin-Like Growth Factor I Display Sexual Dimorphism in Growth Hormone-Stimulated Postnatal Growth. Endocrinology 141: 4436-4441 [Abstract] [Full Text]  
• Ong, K., Kratzsch, J., Kiess, W., Costello, M., Scott, C., Dunger, D. (2000). Size at Birth and Cord Blood Levels of Insulin, Insulin-Like Growth Factor I (IGF-I), IGF-II, IGF-Binding Protein-1 (IGFBP-1), IGFBP-3, and the Soluble IGF-II/Mannose-6-Phosphate Receptor in Term Human Infants. J. Clin. Endocrinol. Metab. 85: 4266-4269 [Abstract] [Full Text]  
• Ballinger, A B, Azooz, O, El-Haj, T, Poole, S, Farthing, M J G (2000). Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis. Gut 46: 695-700 [Abstract] [Full Text]  
• Woods, K. A., Camacho-Hübner, C., Bergman, R. N., Barter, D., Clark, A. J. L., Savage, M. O. (2000). Effects of Insulin-Like Growth Factor I (IGF-I) Therapy on Body Composition and Insulin Resistance in IGF-I Gene Deletion. J. Clin. Endocrinol. Metab. 85: 1407-1411 [Abstract] [Full Text]  
• Rasmussen, S. K., Lautier, C., Hansen, L., Echwald, S. M., Hansen, T., Ekstrøm, C. T., Urhammer, S. A., Borch-Johnsen, K., Grigorescu, F., Smith, R. J., Pedersen, O. (2000). Studies of the Variability of the Genes Encoding the Insulin-Like Growth Factor I Receptor and Its Ligand in Relation to Type 2 Diabetes Mellitus. J. Clin. Endocrinol. Metab. 85: 1606-1610 [Abstract] [Full Text]  
• Liu, J.-L., Yakar, S., LeRoith, D. (2000). Conditional Knockout of Mouse Insulin-Like Growth Factor-1 Gene Using the Cre/loxP System. Exp. Biol. Med. 223: 344-351 [Abstract] [Full Text]  
• Van Wyk, J. (1999). Insulin-Like Growth Factors and Skeletal Growth: Possibilities for Therapeutic Interventions. J. Clin. Endocrinol. Metab. 84: 4349-4354 [Full Text]  
• LeRoith, D. (1999). Insulin-like Growth Factors in Pediatric Health and Disease. J. Clin. Endocrinol. Metab. 84: 4355-4361 [Full Text]